{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:44:19Z","timestamp":1791524659777,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201016071796"],"award-info":[{"award-number":["RS\u20102025\u201016071796"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Skeletal muscle atrophy is a common condition caused by numerous factors, such as aging (termed sarcopenia), disease (e.g., cancer cachexia) or specific medications (such as glucocorticoids). There is no FDA\u2010approved drug for treating skeletal muscle atrophy. Previously, clinical studies had highlighted the anti\u2010diabetic properties of\n Gymnema inodorum<\/jats:italic>\n extract, an indigenous medicinal plant and functional food in Thailand. However, these studies did not identify the active compound(s) responsible for its therapeutic effects. This research aimed to identify safe natural product\u2010derived compounds from clinically relevant plants such as\n Gymnema inodorum<\/jats:italic>\n that bridge the connection between metabolic diseases and skeletal muscle atrophy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Utilizing the dexamethasone (Dex) induced skeletal muscle atrophy model, the major active compounds were isolated using bioactivity\u2010guided screening. The chemical structure of active compound(s) was elucidated using various spectroscopic methods, including HRESIMS, 1D and 2D NMR. Active compound(s) were tested in cell\u2010based and murine models of skeletal muscle atrophy. Insulin signaling and autophagy activity were assessed by western blotting and the mRFP\u2010GFP\u2010LC3 (ptf\u2010LC3) probe. Docking studies determined the binding affinities of active compound(s) for the insulin and glucocorticoid receptors.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We determined a new, previously undescribed methyl anthranilate\u2010conjugated oleanane bioactive compound, termed gymnemantoside A. Treatment with gymnemantoside A recovered myotube diameter and skeletal muscle fibre CSA in atrophy models and downregulated expression of the atrogenes, atrogin\u20101 and MuRF\u20101 (myotube diameter: +33.82%,\n p<\/jats:italic>\n \u2009<\u20090.05, CSA: +128%,\n p<\/jats:italic>\n \u2009<\u20090.01; atrogin\u20101: \u221258.70%, MuRF\u20101: \u221257.32%,\n p<\/jats:italic>\n \u2009<\u20090.05). Gymnemantoside A also reduced autophagy levels both in\u00a0vitro and in\u00a0vivo (\u221265.56%,\n p<\/jats:italic>\n \u2009<\u20090.01), increased expression of insulin growth factor\u20101 (+78.05%,\n p<\/jats:italic>\n \u2009<\u20090.05) and the insulin receptor (+56.42%,\n p<\/jats:italic>\n \u2009<\u20090.05), and recovered activity of the downstream Akt\/mTOR\u2010mediated insulin signalling pathway. Molecular docking analysis with gymnemantoside A and standard receptor ligands revealed that gymnemantoside A could interact with the insulin receptor tyrosine kinase and prevent Dex binding with the glucocorticoid receptor. In the murine atrophy model, gymnemantoside A treatment enhanced exercise endurance in the rotarod test (+260%,\n p<\/jats:italic>\n \u2009<\u20090.05) and the mass of the predominantly fast fibre type TA muscle (+116%,\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A newly identified bioactive compound gymnemantoside A, isolated from\n Gymnema inodorum<\/jats:italic>\n , was structurally characterized and showed efficacy in Dex\u2010induced muscle atrophy models. Gymnemantoside A produces anti\u2010muscle atrophy effects by a hitherto unreported mechanism: modulation of the insulin receptor kinase domain and activation of downstream signalling, alongside competitive inhibition of the glucocorticoid receptor, which has been implicated in multiple forms of skeletal muscle wasting.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70118","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T02:59:30Z","timestamp":1764125970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gymnemantoside A Ameliorates Steroid\u2010Induced Skeletal Muscle Atrophy via Bridging Glucocorticoid and Insulin Receptor Signalling"],"prefix":"10.1002","volume":"16","author":[{"given":"Eun\u2010Jin","family":"Park","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of Life Sciences and Medical Engineering, New Drug Targets Laboratory Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of Life Sciences and Medical Engineering, New Drug Targets Laboratory Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seri","family":"Choi","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi\u2010Phuong","family":"Doan","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung\u2010Hwan","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of Life Sciences and Medical Engineering, New Drug Targets Laboratory Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Pyo","family":"An","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Woon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of Life Sciences and Medical Engineering, New Drug Targets Laboratory Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2555-3069","authenticated-orcid":false,"given":"Darren\u00a0Reece","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of Life Sciences and Medical Engineering, New Drug Targets Laboratory Gwangju Institute of Science and Technology Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won\u00a0Keun","family":"Oh","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy Seoul National University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"2","key":"e_1_2_7_2_1","first-page":"565","article-title":"Research on the Elderly: Economic Status, Retirement, and Consumption and Saving","volume":"28","author":"Hurd M. 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